LINKAGE ANALYSIS AND IDENTIFICATION OF DELETION IN ALAGILLE-SYNDROME GENE

Alagille syndrome (AGS) is a generic disease and the responsible gene has already been mapped at 20p12. To more accurately detect the region of the AGS gene on the linkage map of chromosome 20p, 14 yeast artifi cial chromosome (YAC) clones were screened to construct a YAC contig i n the candidate region and 13 locus markers and 2 sequence-tagged site s (STS) were ordered. Combining all of the analyses, a 1.3 Mb critical region from D20S507 to D20S61 for the ACS gene was identified. As the human Jagged 1 gene (JAG1) lies just in this region and is responsibl e for the AGS disease, the genomic DNA in an AGS family without a visi ble deletion were analyzed by single-strand conformational polymorphis m (SSCP) and direct DNA sequencing, and a 2-bp (CT) deletion mutation at exon 26 of the JAG1 was identified.